Involvement of GABAergic transmission in the midbrain ventral tegmental area in the regulation of hippocampal theta rhythm

Previously we indicated that the ventral tegmental area (VTA) may belong to the system regulating hippocampal theta rhythm. In the present study, we aimed at assessing the role of the GABAergic system of the VTA in regulation of hippocampal electric activity. Male Wistar rats received unilateral intra-VTA microinjection of either bicuculline (50 ng/0.5 μl, n = 9), muscimol (100 ng/0.5 μl, n = 10) or phaclofen (500 ng/0.5 μl, n = 9). 1-min tail pinch stimulations were applied at 10-min intervals to evoke theta rhythm episodes in hippocampus. We analysed peak power (Pmax) and corresponding frequency (Fmax) of EEG signal at delta and theta bands. Bicuculline induced theta rhythm in both hippocampi with 0 latency, continuous for ca. 33 min. Phaclofen also induced theta but in this group it appeared with latency (17.45 ± 3.16 min on average), lasted for ca. 33.6 min and during this time was interrupted by periods of irregular activity of variable length. Tail pinch was not applied in these groups. Muscimol induced an opposite effect: depression of theta Pmax with simultaneous increase in delta Pmax and a decrease in Fmax delta during episodes of tail pinch-evoked theta. This effect had variable latency and no return to the control EEG could be observed. We propose that GABA activity in the VTA is of tonic character, so that abolition of this mechanism produces immediate effect, i.e. theta induction (strong by GABAA and weak by GABAB receptors blockade), whereas enhancing the alread